硫代乙酰胺致小鼠肝性脑病模型的建立及评估

目的：探讨应用硫代乙酰胺（TAA）和C57/BL6小鼠制备肝性脑病模型的方法。方法100只小鼠分成4组，对照组（A组）、实验组B、C、D组，每组25只，分别予生理盐水和TAA 100、200、300 mg/（kg·d）腹腔内注射。注射药物后每24小时通过旷场实验、ROTA ROD实验及神经功能学评分检测神经功能，观察肝组织病理变化。结果旷场试验中，与对照组相比，从造模第1天开始，各实验组小鼠均出现运动总路程和总时间明显下降（P 〈0.05），而各实验组之间无明显差异。 ROTA ROD实验中，与对照组相比，造模第3天实验D组小鼠运动时间明显下降（P =0.036）；第4天，各实验组小鼠均明显下降（P =0.000），而实验组内无明显差异。造模第4天，实验C、D组小鼠神经功能学评分平均值分别为6.3和5.1分，与对照组比较，差异有统计学意义（P 〈0.05）。造模第4天实验B、C、D 3组小鼠的累积生存率分别为71.4%、71.4%和42.9%。3组实验组小鼠肝组织病理改变均符合急性肝衰竭改变。结论 C57/BL6小鼠采用TAA可成功制备肝性脑病动物模型，200 mg/（kg＆#183;d）TAA腹腔注射，连续4 d，为推荐方法。

Hepatic encephalopathy in mice model induced by thioacetamide

Objective To explore the suitable method of establishing model of hepatic encephalopathy （HE） by thioacetamide （TAA） in C57/BL6 mice. Methods HE was induced in mice （C57/BL6）by TAA in this study. One hun-dred mice were divided into 4 groups. The control group was given 0.9% saline, the other 3 study groups were given 100, 200 and 300 mg/（kg·d） TAA by intra-peritoneal injections respectively. The open field test, ROTA ROD test, neuro-logical function test and liver pathology were performed to evaluate the mice model. Results The mice in the study groups significantly declined in total distances and moving duration of open field test than those in the control group （P 〈 0.05）, but there were no differences among the 3 study groups. In the ROTA ROD test on the third day after establishing the model,the mean moving time of mice in the 300 mg/（kg＆#183;d） dosage group declined significantly （P = 0.036）, compared with the control group. And all the mice in the study groups showed significant differences than those in the control group on the fourth day（P =0.000）. The average neurological function scores were 6.3 and 5.1 respectively in the 200 mg/（kg·d） and 300 mg/（kg·d） groups on the fourth modeling day, which were less than that in the control group （P 〈0.05）. The cu-mulative survival rates of mice in groups of 100 mg/（kg·;d）, 200 mg/（kg·d） and 300 mg/（kg·d） were 71.4%、71.4% and 42.9%respectively on the fourth day. Pathological analysis showed that all liver tissues of mice received TAA exhibited the characteristic changes of acute liver failure. Conclusion HE model of C57/BL6 mice induced by 200 mg/（kg·;d） of TAA appears to be suitable for the study of the pathogenesis of HE.